1. Field of the Invention
This invention relates to the field of medical devices, such as stents. More particularly, this invention is directed to coatings which include chemically-bound polymers and/or oligomers of L-arginine.
2. Description of Related Art
In the field of medical technology, there is frequently a necessity to administer drugs locally. To provide an efficacious concentration to the treatment site, systemic administration of medication often produces adverse or toxic side effect for the patient. Local delivery is a preferred method in that smaller total levels of medication are administered in comparison to systemic dosages, but are concentrated at a specific site. Thus, local delivery produces fewer side effects and achieves more effective results.
A commonly employed technique for the local delivery of a drug is through the use of a medicated stent. One method of medicating a stent is by coating the stent with a polymer having a drug incorporated therein. L-arginine, or polypeptide oligomeric derivatives thereof, for example, those containing 5 to 20 amino acid units, is one example of a substance that can be delivered via a stent.
L-arginine is known to be a precursor of endothelium derived nitric oxide (NO). NO is synthesized from L-arginine, or its polymeric and/or oligomeric derivatives, by the enzyme NO synthase oxygenase, a homodimeric flavo-hemoprotein that catalyzes the 5-electron oxidation of L-arginine to produce NO and L-citrulline. Among other therapeutic properties, NO relaxes vascular smooth muscle cells and inhibits their proliferation. References describing beneficial therapeutic properties of L-arginine include U.S. Pat. No. 5,861,168 to Cooke et al. Cooke et al. teach that administering L-arginine, as the NO precursor, restores vascular NO activity in patients with endothelial vasodilator dysfunction due to restenosis. Moreover, Uemura et al. (Circulation, vol. 102, 2629–2635 (2000)), teach that the heptamer of L-arginine (R7) exhibits biological activity in the reduction of neointimial hyperplasia.
According to traditional techniques, L-arginine or its polymers and/or oligomers can be physically incorporated into a polymeric matrix for in situ local delivery. The embodiments of the present invention provide alternative methods for local delivery of L-arginine, or its polymers and/or oligomers, by an implantable device such as a stent.